Recent evidence indicates that the abilities of malignant tumor cells to invade adjacent tissues and form secondary tumor colonies at distant host sites are determined, in part, by cell surface properties. Model systems have been developed such as the series of variant B16 melanoma sublines selected in vivo for enhanced colonization of lung, brain, or ovary as well as sublines selected in vitro for enhanced tissue invasion and other properties. We will determine the cell surface and other characteristics of B16 melanoma sublines and clones and human A375 melanoma sublines and clones of different metastatic potentials including surface glycoproteins, proteoglycans, enzymes, antigens, and other components that may be involved in invasive and metastatic properties. Biochemical, immunological, enzymatic, and ultrastructural techniques will be used to study melanoma cells grown in vitro and in vivo. Adhesive and invasive properties will be examined using target and nontarget-derived endothelial cells, endothelial cell basal lamina-like matrix, and organ tissue. The dynamics and stabilities of cell surface components including their distribution and shedding into the extracellular environment will be studied in relation to malignant characteristics. Plasma membrane vesicles will be isolated, and they or their glycoprotein components will be utilized to construct targeting liposomes in order to direct antitumor agents to specific organ sites where metastases are confirmed or are likely. (A)